Support is requested for a Keystone Symposia meeting entitled The Hippo Tumor Suppressor Network: From Organ Size Control to Stem Cells and Cancer, organized by Marius Sudol, Helen McNeill, Georg A. Halder and Giovanni Blandino. The meeting will be held in Monterey, California from May 19 - 23, 2013. The general topic of this meeting is relevant to the NCI mission with respect to research into the development of new cancer therapies. Moreover, most of the speakers invited to speak at the symposium are basic cancer researchers who have been supported by NCI. Over the past several years, the Hippo tumor suppressor pathway has emerged as a complex signaling network that has significant implications for our understanding of the molecular mechanisms of cancer development and stem cell biology. The main effectors of this pathway, YAP and TAZ, are transcriptional co- activators, which act as stemness factors and potent oncogenes. Recent studies have revealed that abnormal expression of components of the network can lead to cancer. Therefore, the pathway and its networking molecules are attractive targets for the development of cancer drugs and unconventional therapeutic interventions. Several paradoxes have emerged in the field in recent years, and fast progress in this field is due, in large part, t an active dialog between Drosophila geneticists and mammalian signalers. The overwhelming interest of researchers in the function of the Hippo pathway in stem cells and cancer prompted us to seek a larger forum. At the Keystone Symposia meeting on The Hippo Tumor Suppressor Network we aim to: (i) Define why YAP and TAZ function as either oncogenes or tumor suppressors; (ii) Identify membrane complexes, which activate the Hippo pathway in mammals, as the orthology with the fly receptors is not clear; (iii) Define targets for small molecule inhibitors and activators within pathway components based on structured modules, including WW, PDZ and SARAH domains. The meeting will be unique in bringing together Drosophila geneticists, basic and clinical cancer researchers, and the stem cell research community. We anticipate that this meeting will help to consolidate the emerging field and have an impact on development of new cancer therapies.